Biology subjects

Moretti, S.

Publications and source records attributed to Moretti, S..

13 recordsLinked to original sources

bioRxiv2026

Plasma oxytocin measured by LC-MS/MS varies with life stage, sex, and obesity in mice

ObjectiveOxytocin (Oxt) assessment in plasma is challenging, and available data are contradictory. We aimed to assess circulating Oxt in mice by a validated nano-liquid chromatography/mass-spectrometry (nLC-MS/MS) protocol, combined with Oxt hypothalamic expression in different sex, life stages, and in diet-induced obesity. MethodsWe assessed plasma Oxt by nLC-MS/MS, Oxt hypothalamic expression by qPCR, and Oxt-immunoreactive neuron and fiber densities by immunohistochemistry and morphometric analyses in C57BL/6 mice at 21 and 60 days of life (p21 and p60, respectively). Mice in normo-fed condition and following 12 weeks of high-fat diet (HFD) were studied alongside food intake and hypothalamic expression of its regulators. ResultsCirculating Oxt does not vary based on sex at p21 and p60 but increases with aging. While hypothalamic Oxt mRNA expression followed the same trend across both sexes, Oxt neuron and fiber densities exhibited a similar trend only in females. Plasma vasopressin (Avp) followed Oxt trend in females but was opposite in males and was not mirrored by Avp mRNA hypothalamic expression. HFD-fed females were more resistant to weight gain compared to males and displayed higher Oxt plasma levels and hypothalamic expression. Sex dimorphism in food intake and hypothalamic expression of Avp and of key anorexigenic and orexigenic neuropeptides was detected. ConclusionsOxt plasma levels are higher in adulthood compared to weaning in mice of both sexes who displayed similar concentrations. Oxt plasma levels are mirrored by Oxt hypothalamic expression. In obesity, females display a lower increase in body weight but higher Oxt plasma levels than males. SignificanceThis study delineates the pattern of Oxt plasma levels across various age, sex and in obesity in mice. We overcome some limitations of previous research, which were often confounded by numerous factors, by reliably measuring circulating Oxt and integrating this with parallel analyses of Oxt gene expression, and Oxt neuron and immunoreactive fiber densities. Critically, this is among the few studies to employ LC-MS/MS specifically in mice. This novel, integrated perspective is relevant given the compelling evidence for Oxts role as an anti-obesity agent and its potential as a therapeutic target. A precise understanding of Oxt regulation in different conditions, backed by reliable methodologies, is indispensable for the rational development of effective treatments for obesity and related endocrine diseases.

neuroscience↗

bioRxiv2026

Patterns of molecular conservation along tooth development are only partly shaped by evolutionary pressures on tooth

Although it is well established that certain stages of development are molecularly more conserved than others, the reasons for this phenomenon remain largely unknown. We study molecular conservation in the development of an organ, the molar, by comparing the temporal profiles of expression in mice and hamsters. We find that the cause of conservation of expression and of coding sequences changes over molar development. Gene expression levels display a classical increase of divergence as development progresses. In terms of genes expressed, the composition of early and late stages is better conserved and enriched in pleiotropic genes, yet each stage mobilizes different sets of pleiotropic genes, cell division for bud growth and secretion for tooth mineralization. Moreover similar patterns of higher divergence of gene sets and of coding sequences at mid development, are caused by different biological phenomena, in that case heterochronies and blood colonisation respectively. In conclusion, the patterns of molecular conservation in developing molars are shaped by a combination of processes intrinsic to the teeth, and by negative and positive selection on functions which are mostly extrinsic to the teeth. This is likely translatable to explain molecular conservation patterns in many other biological systems. AUTHOR SUMMARYFor species to evolve different adaptations to different life styles, their anatomy has to evolve correspondingly. This in turn implies evolution of the embryonic development of anatomical structures. Notably, tooth shape can evolve rapidly as an adaptation to different diets. Mice and hamsters are closely related rodents who yet differ in the shape of their molars, and thus in their development. In this study, we investigated why the genes active in molar development are more or less similar between the two species from early tooth bud to fully formed embryo molar. We found that early and late molar development were slow evolving, while mid-development was evolving faster. But surprisingly, this was in part due not to tooth evolution, but to the involvement of genes which are active in other processes in the body. For example an influx of immune cells also brings fast evolving immune genes. This helps us understand better the complexity of causes of apparently simple evolutionary patterns.

evolutionary biology↗

bioRxiv2025

Investigating the intraspecific diversity of Vitis vinifera responses to esca with a physiopathology approach

Woody plant dieback involves complex interactions between pathogens, plant functional traits and environmental conditions. The role of intraspecific variation in functional strategies in shaping susceptibility to dieback remains unclear, despite its importance for understanding plant adaptation to changing environments. We used a common garden containing 46 Vitis vinifera (grapevine) cultivars to test the hypothesis that differences in grapevine susceptibility to esca, a complex vascular disease leading to dieback, result from intraspecific syndromes of leaf gas exchange, wood anatomical and metabolic traits, and microbiome. Cultivars with conservative water use strategies tended to be less susceptible to esca whereas xylem anatomy did not affect esca susceptibility. Across cultivars, symptomatic plants displayed decreases in leaf gas exchange, stem starch storage and theoretical hydraulic conductivity in response to esca. Symptomatic stems accumulated more secondary metabolites (mostly glycosylated flavonoids and terpenes) in highly susceptible than in weakly susceptible genotypes, whereas stem microbial communities were unaffected. This suggests that disease expression is linked to cultivar-specific metabolic responses. Intraspecific variation in physiological strategies contributes to differences in susceptibility to a complex vascular disease. Integrative studies unravelling plant-microorganism-environment interactions are crucial to improve our understanding of complex plant diseases.

plant biology↗

bioRxiv2025

StereoMapper: Clarifying Metabolite Identity Through Stereochemically Aware Relationship Assignment

Inaccuracies in metabolite cross-mapping frequently introduce errors into genome-scale metabolic models (GEMs). A key challenge lies in distinguishing truly identical metabolites from closely related structural variants, such as stereoisomers, across biochemical databases. StereoMapper addresses this issue by establishing stereochemically aware relationships that clarify metabolite identity. It operates entirely on structural information, using molecular structures to infer equivalence and define relationships. StereoMapper was implemented using RDKit (2025.3.3) and Open Babel-wheel (3.1.1.22) which provides the core functionality of the Open Babel software, and benchmarked across four curated control datasets to evaluate performance in relationship classification (enantiomer, diastereomer, stereo-resolution pairs, and protomer). The pipeline was subsequently applied to 1.3 million molecular structures from multiple metabolic databases to generate equivalent isomeric sets (groups of structures identified as equivalent by StereoMapper). These sets were compared against the human subset of MetaNetX, a context-aware reference, to assess concordance and investigate disagreements. On curated positive control sets containing only positive examples across multiple relationship classes, StereoMapper achieved mean precision, recall, and F1-scores of 92.6, 98.0, and 95.3, respectively; following optimisation, these improved to 98.9, 98.2, and 98.5. Application to the 1.3 million structures produced over 339,000 stereochemically defined relationships between molecular structures. Comparison with the human subset of MetaNetX assignments showed an overall grouping concordance of 93.5%. The remaining 6.5% of differences were mainly associated with protomer relationships (52.3%) and stereo-resolution pairs (37.4%), while 21.6% involved complex or ambiguous cases. Scientific contribution statementStereoMapper provides a stereochemically aware pipeline for metabolite relationship assignment that shows high performance across multiple benchmark datasets, resolving key ambiguities in metabolite identity and providing a complementary approach to existing context-aware frameworks. Its integration will enhance reaction-level cross-mapping and improve the accuracy of future GEM reconstructions.

systems biology↗

bioRxiv2025

Stress-dependent responses of grapevine wood and fungal pathogen activity under esca and drought

O_LIBiotic and abiotic stresses alter the physiology of perennial plants, with consequences for fungal endophytes and disease expression. In grapevine, one of the worlds most valuable crops, drought inhibits esca disease expression, but the underlying molecular interactions between plant and fungi are unknown. C_LIO_LIWe combined wood metatranscriptomics, metabolomics, and metabarcoding to investigate these interactions in 30-year-old grapevines and eight wood-pathogenic fungi under conditions of drought or esca leaf symptom expression. C_LIO_LIBoth esca and drought decreased grapevine transpiration, but with different transcriptomic and metabolic signatures. Similar pathways were also activated, including the phenylpropanoid and stilbenoid synthesis pathways. These stress responses could potentially confer cross-tolerance, and elicit different fungal molecular responses. The levels of putative fungal virulence factors increased significantly under both stresses. Under drought, only the relative abundance of Phaeomoniella chlamydospora and gene expression involved in anti-oxidative mechanisms, growth, and reproduction increased. Under esca expression conditions, only the relative abundance of Fomitiporia mediterranea and gene expression involved in wood degradation, competition, detoxification, and growth increased. C_LIO_LIThe grapevine defense mechanisms induced by drought coupled with a low transpiration rate and a low abundance and virulence of F. mediterranea may account for esca leaf symptom inhibition upon water deficit. C_LI

plant biology↗

bioRxiv2025

Differential impacts of drought and esca expression on Ascomycota fungi in the trunks and young organs of mature grapevines

Perennial plant decline is increasingly threatening the profitability and sustainability of agriculture and forestry worldwide. It results from intricate interactions between microbial communities, the plant host, and abiotic stressors. We investigated the effects of drought and esca disease on mature grapevine phytobiomes. Grapevines display no esca leaf symptoms during droughts, but the impacts of drought and esca expression on fungal communities and wood health in mature plants remain poorly understood. We studied 43 uprooted 30-year-old naturally infected vines in three experimental conditions: well-watered asymptomatic (Control) vines, vines with esca symptoms (Esca), and vines subjected to water deficit (WD) over two consecutive summers. We profiled trunk, cane, stem and petiole Ascomycota communities by DNA metabarcoding with primers specifically designed for grapevine trunk-associated Ascomycota, and quantified wood necrosis. The Ascomycota communities of trunks and younger organs clearly differed, and drought and esca had different impacts on the Ascomycota communities of perennial and young organs. In the trunk, drought significantly decreased fungal diversity in healthy wood and increased the abundance of wood pathogens (e.g. Phaeomoniella chlamydospora, Botryosphaeria dothidea). In young organs, esca expression decreased the species richness and diversity of the Ascomycota community to a greater extent than drought. We also found that the relative proportion of healthy wood was smaller in plants with esca symptoms than in control plants. Thus, drought increased Ascomycota pathogen abundance in the trunk but did not increase wood degradation and esca expression, highlighting the need to investigate the molecular basis of plant-microbiome interactions under multi-stress conditions.

plant biology↗

bioRxiv2025

Inverse hourglass pattern of conservation in rodent molar development.

Although it is well established that certain stages of development are more conserved than others, the reasons for this phenomenon remain largely unknown. We study molecular conservation in the development of an organ, the molar, by comparing the temporal profiles of expression in mice and hamsters. We find that molar development is characterized by a rarely observed pattern of conservation of expression level and coding sequences forming an inverse hourglass, with more conservation at the beginning and end of morphogenesis than at intermediate stages. As the development of the rodent molar is well described, we were able to link this pattern to the properties of the expressed genes and the activity of different developmental processes. Early and late stages mobilize different sets of pleiotropic genes, cell division for bud growth and secretion for tooth mineralization. The particularities of dental morphogenesis and homeostasis, with the degradation of certain tissues at the end of development and the hosting of immune cells, as well as heterochronies linked to adaptations, also probably contribute to the pattern. Our study of the different actors explains the inverted hourglass of molars by a combination of processes intrinsic to the teeth, and by negative and positive selection which is mostly extrinsic to the teeth. This is likely translatable to explain molecular conservation patterns in many other biological systems.

evolutionary biology↗

bioRxiv2024

Inter-individual gene expression variability implies stable regulation of brain-biased genes across organs

Phenotypic variation among individuals provides the raw material for evolution, and gene expression is a key mediator between genetic and phenotypic variation. As for phenotypes, the range of gene expression is limited and biased by evolutionary and developmental constraints. Observed expression variability due to biomolecular stochasticity and cell-to-cell heterogeneity has been well-studied in isogenic populations of unicellular organisms. However, for multicellular organisms with a diversity of cells and tissues sharing the same genetic background, the interplay between expression variability, gene and organ function, and gene regulation remains an open question. Here, we use highly multiplexed 3-end bulk RNA sequencing to generate transcriptome profiles spanning at least nine organs in outbred individuals of three ray-finned fish species: zebrafish, Northern pike, and spotted gar. Per organ, we quantify individual-to-individual gene expression variability independent of mean expression level. Lowly variable genes are enriched in cellular housekeeping functions whereas highly variable genes are enriched in stimulus-response functions. Furthermore, highly variable genes evolve under weaker purifying selection at the protein-coding sequence, indicating that intra-species expression variability predicts inter-species protein sequence divergence. Genes that are broadly expressed across organs are both highly expressed and lowly variable, whereas organ-biased genes are typically highly variable within their top organ. Among organ-biased genes, patterns of expression variance are dependent on the top organ. Specifically, brain- and gonads-biased genes have lowly variable expression across different organs, suggesting stabilizing selection. These patterns suggest that gene regulatory mechanisms evolve under organ-specific selective pressures.

evolutionary biology↗

bioRxiv2020

A cell-autonomous PD-1/PD-L1 circuit promotes tumorigenicity of thyroid cancer cells by activating a SHP2/Ras/MAPK signalling cascade

The programmed cell death-1 (PD-1) and its ligands PD-L1 and PD-L2 are immune checkpoints. Typically, cancer cells express the PD-Ls that bind PD-1 on immune cells, inhibiting their anti-cancer activity. Recently, PD-1 expression has been found in cancer cells. We analysed expression and functions of PD-1 in thyroid cancer (TC). Human TC specimens (47%), but not normal thyroids, displayed PD-1 expression in epithelial cells, which significantly correlated with tumour stage and lymph-node metastasis. PD-1 overexpression/stimulation promoted TC cell proliferation and migration in culture. PD-1 recruited the SHP2 phosphatase, potentiated its phosphatase activity thus enhancing Ras activation by dephosphorylation of inhibitory tyrosine 32 and triggering the MAPK cascade. PD-1 inhibition decreased, while PD-1 overexpression facilitated, TC cell xenograft growth by affecting cell proliferation. PD-1 circuit blockade in TC, besides restoring anti-cancer immunity, could also directly impair TC cell growth by inhibiting the Ras/MAPK pathway.

cancer biology↗

bioRxiv2020

MetaNetX/MNXref - unified namespace for metabolites and biochemical reactions in the context of metabolic models

MetaNetX/MNXref is a reconciliation of metabolites and biochemical reactions providing cross-links between major public biochemistry and Genome-Scale Metabolic Network (GSMN) databases. The new release brings several improvements with respect to the quality of the reconciliation, with particular attention dedicated to preserving the intrinsic properties of GSMN models. The MetaNetX website (https://www.metanetx.org/) provides access to the full database and online services. A major improvement is for mapping of user-provided GSMNs to MXNref, which now provides diagnostic messages about model content. In addition to the website and flat files, the resource can now be accessed through a SPARQL endpoint (https://rdf.metanetx.org).

systems biology↗

bioRxiv2020

The Bgee suite: integrated curated expression atlas and comparative transcriptomics in animals

Bgee is a database to retrieve and compare gene expression patterns in multiple animal species, produced by integrating multiple data types (RNA-Seq, Affymetrix, in situ hybridization, and EST data). It is based exclusively on curated healthy wild-type expression data (e.g., no gene knock-out, no treatment, no disease), to provide a comparable reference of normal gene expression. Curation includes very large datasets such as GTEx (re-annotation of samples as "healthy" or not) as well as many small ones. Data are integrated and made comparable between species thanks to consistent data annotation and processing, and to calls of presence/absence of expression, along with expression scores. As a result, Bgee is capable of detecting the conditions of expression of any single gene, accommodating any data type and species. Bgee provides several tools for analyses, allowing, e.g., automated comparisons of gene expression patterns within and between species, retrieval of the prefered conditions of expression of any gene, or enrichment analyses of conditions with expression of sets of genes. Bgee release 14.1 includes 29 animal species, and is available at https://bgee.org/ and through its Bioconductor R package BgeeDB.

bioinformatics↗

bioRxiv2017

Gene set enrichment analysis using RNA-seq-based condition-specific metabolic networks

MotivationGenome-scale metabolic networks and transcriptomic data represent complementary sources of knowledge about an organisms metabolism, yet their integration to achieve biological insight remains challenging.\n\nResultsWe investigate here condition-specific series of metabolic sub-networks constructed by successively removing genes from a comprehensive network. The optimal order of gene removal is deduced from transcriptomic data. The sub-networks are evaluated via a fitness function, which estimates their degree of alteration. We then consider how a gene set, i.e. a group of genes contributing to a common biological function, is depleted in different series of sub-networks to detect the difference between experimental conditions. The method, named metaboGSE, is validated on public data for Yarrowia lipolytica and mouse. It is shown to produce GO terms of higher specificity compared to popular gene set enrichment methods like GSEA or topGO.\n\nAvailabilityThe metaboGSE R package is available at https://cran.r-project.org/web/packages/metaboGSE.

systems biology↗

bioRxiv2017

Taxon sampling unequally affects individual nodes in a phylogenetic tree: consequences for model gene tree construction in SwissTree

Medium to large phylogenetic gene trees constructed from datasets of different species density and taxonomic range are rarely topologically consistent because of missing phylogenetic signal, non-phylogenetic signal and error. In this study, we first use simulations to show that taxon sampling unequally affects nodes in a gene tree, which likely contributes to controversial conclusions from taxon sampling experiments and contradicting species phylogenies such as for the boreoeutherians. Hence, because it is unlikely that a large gene tree can be reconstructed correctly based on a single optimized dataset, we take a two-step approach for the construction of model gene trees. First, stable and unstable clades are identified by comparing phylogenetic trees inferred from multiple datasets and data types (nucleotide, amino acid, codon) from the same gene family. Subsequently, data subsets are optimized for the analysis of individual uncertain clades. Results are summarized in form of a model tree that illustrates the evolutionary relationship of gene loci. A case study shows how a seemingly complex gene phylogeny becomes increasingly consistent with the reference species tree by attentive taxon sampling and subtree analysis. The procedure is progressively introduced to SwissTree (http://swisstree.vital-it.ch), a resource of high confidence model gene (locus) trees. Finally we demonstrate the usefulness of SwissTree for orthology benchmarking.

bioinformatics↗